H-ras activation is an early event in the ptaquiloside-induced carcinogenesis: Comparison of acute and chronic toxicity in rats

Bracken fern (Pteridium spp.) produces cancer of the urinary bladder and oesophagus in grazing animals and is a suspected human carcinogen, The carcinogenic principle ptaquiloside (PT), when activated to a dienone (APT), forms DNA adducts which eventually leads to tumor. Two groups of female Sprague-Dawley rats were given a chronic dose of 3 mg APT weekly for 10 weeks either by intravenous (iv) tail vein or by intragastric (ig) route, A third group was given a weekly dose of 6 mg of APT for 3 weeks by the ig route corresponding to acute dosing. Both chronic iv and ig dosed animals showed ischemic tubular necrosis in the kidney but only iv dosed animals developed adenocarcinomas of the mammary glands. Acutely dosed ig animals produced apoptotic bodies in the liver, necrosis of blood cell precursors in the bone marrow and ischemic tubular necrosis in the kidney but they did not develop tumors, No mutations were found in the H-ras and p53 genes in the mammary glands of either the ig rats or the tumor-bearing iv rats. However, the mammary glands of a fourth group of rats, which received APT by iv and killed before tumor development, carried Pu to Pu and Pu to Py double mutations in codons 58 and 59 of H-ras. This study indicates that the route of administration plays a role in the nature of the disease expression from ptaquiloside exposure. In addition to confirming the role of APT in the PT-induced carcinogenesis our finding suggests that activation of H-ras is an early event in the PT-carcinogenesis model. (C) 1998 Academic Press.

Leaking urine in Australian women: Prevalence and associated conditions

The paper aims to (1) assess the prevalence of leaking urine and to (2) explore associations between leaking urine and a variety of other symptoms, conditions, surgical procedures and life events in three large cohorts of Australian women, who are participants in the Australian Longitudinal Study on Women's Health. Young women aged 18-23 (N = 14,000), mid-age women, 45-50 (N 13,738) and older women, 70-75 (N = 12,417), were recruited randomly from the national HIC/Medicare database. Leaking urine was reported by approximately one in eight young women [estimated prevalence 12.8% (95% CI: 12.2-13.3)] and one in three mid-age women [36.1% (CI: 35.2-37.0)] and older women [35.0% (CI: 34.1-35.9)]. Leaking urine was significantly associated with parity, conditions which increase the pressure on the pelvic floor such as constipation and obesity, past gynecological surgery and conditions which can impact on bladder control. The study showed that fewer than half the women had sought help for the problem and that younger women were less likely to be satisfied with the help available for this problem. Strategies for continence promotion, including opportunistic raising of the issue at the time of cervical screening and pregnancy care are suggested, so that the health and social outcomes of untreated chronic incontinence in women might be improved.

Ca2+ sensitivity of phospholipid scrambling in human red cell ghosts

The phospholipids in plasma membranes of erythrocytes, as well as platelets, lymphocytes and other cells are asymmetrically distributed, with sphingomyelin and phosphatidylcholine residing predominantly in the outer leaflet of the bilayer, and phosphatidylserine and phosphatidylethanolamine in the inner leaflet. It is known that Ca2+ can disrupt the phospholipid asymmetry by activation of a protein known as phospholipid scramblase, which affects bidirectional phospholipid movement in a largely non-selective manner. As Ca2+ also inhibits aminophospholipid translocase, whose Mg2+-ATPase activity is responsible for active translocation of aminophospholipids from the outer to the inner leaflet, it is important to accurately determine the sensitivity of scramblase to intracellular free Ca2+. In the present study we have utilized the favourable K-d, of Mag-fura-2 for calcium in the high micromolar range to determine free Ca2+ levels associated with lipid scrambling in resealed human red cell ghosts. The Ca2+ sensitivity was measured in parallel to the translocation of a fluorescent-labelled lipid incorporated into the ghost bilayer. The phospholipid scrambling was found to be half-maximally activated at 63-88 mu M free intracellular Ca2+. The wider applicability of the method and the physiological implications of the calcium sensitivity determined is discussed.

Leaking urine: Prevalence and associated factors in Australian women

The Women's Health Australia project provided the opportunity to examine the prevalence of leaking urine and associated variables in three large cohorts of Australian women 18-23 years of age (young N = 14,761), 45-50 (mid-age N = 14,070), and 70-75 (older N = 12,893). The proportion of women reporting leaking urine was 12.8% (95% CI: 12.2-13.3), 36.1% (35.2-37.0), and 35% (34.1-35.9) in each of the three cohorts, respectively. Logistic regression analysis showed significant associations between leaking urine and parity in the young and mid-age women, and between leaking urine and constipation, other bowel symptoms, body mass index, and urine that burns or stings in all three groups. in the mid-age and older cohorts, women who reported having both hysterectomy and prolapse repair, or prolapse repair alone, were also more likely to report leaking urine. Lower scores on the physical and mental component summary scores of the medical outcomes survey short form (36 items) questionnaire suggest lower quality of life among women who report leaking urine, compared with those who do not. (C) 1999 Wiley-Liss,Inc.

Assessment of limb muscle and adipose tissue by dual-energy X-ray absorptiometry using magnetic resonance imaging for comparison

OBJECTIVE: To use magnetic resonance imaging (MRI) to validate estimates of muscle and adipose tissue (AT) in lower limb sections obtained by dual-energy X-ray absorptiometry (DXA) modelling. DESIGN: MRI measurements were used as reference for validating limb muscle and AT estimates obtained by DXA models that assume fat-free soft tissue (FFST) comprised mainly muscle: model A accounted for bone hydration only; model B also applied constants for FFST in bone and skin and fat in muscle and AT; model C was as model B but allowing for variable fat in muscle and AT. SUBJECTS: Healthy men (n = 8) and women (n = 8), ages 41 - 62 y; mean (s.d.) body mass indices (BMIs) of 28.6 (5.4) kg/m(2) and 25.1 (5.4) kg/m2, respectively. MEASUREMENTS: MRI scans of the legs and whole body DXA scans were analysed for muscle and AT content of thigh (20 cm) and lower leg (10 cm) sections; 24 h creatinine excretion was measured. RESULTS: Model A overestimated thigh muscle volume (MRI mean, 2.3 l) substantially (bias 0.36 l), whereas model B underestimated it by only 2% (bias 0.045 l). Lower leg muscle (MRI mean, 0.6 l) was better predicted using model A (bias 0.04 l, 7% overestimate) than model B (bias 0.1 l, 17% underestimate). The 95% limits of agreement were high for these models (thigh,+/- 20%; lower leg,+/- 47%). Model C predictions were more discrepant than those of model B. There was generally less agreement between MRI and all DXA models for AT. Measurement variability was generally less for DXA measurements of FFST (coefficient of variation 0.7 - 1.8%) and fat (0.8 - 3.3%) than model B estimates of muscle (0.5-2.6%) and AT (3.3 - 6.8%), respectively. Despite strong relationships between them, muscle mass was overestimated by creatinine excretion with highly variable predictability. CONCLUSION: This study has shown the value of DXA models for assessment of muscle and AT in leg sections, but suggests the need to re-evaluate some of the assumptions upon which they are based.

Localization of N-acetyltransferases NAT1 and NAT2 in human tissues

Human acetyl coenzyme A-dependent N-acetyltransferase (EC 2.3.1.5) (NAT) catalyzes the biotransformation of a number of arylamine and hydrazine compounds. NAT isozymes are encoded at 2 loci; one encodes NAT1, formerly known as the monomorphic form of the enzyme, while the other encodes the polymorphic NAT2, which is responsible for individual differences in the ability to acetylate certain compounds. Human epidemiological studies have suggested an association between the acetylator phenotype and particular cancers such as those of the bladder and colon. In the present study, NAT1- and NAT2-specific riboprobes were used in hybridization histochemistry studies to localize NAT1 and NAT2 mRNA sequences in formalin-fixed, paraffin-embedded human tissue sections. Expression of both NAT1 and NAT2 mRNA was observed in liver, gastrointestinal tract tissues (esophagus, stomach, small intestine, and colon), ureter, bladder, and lung. In extrahepatic tissues, NAT1 and NAT2 mRNA expression was localized to intestinal epithelial cells, urothelial cells, and the epithelial cells of the respiratory bronchioles. The observed heterogeneity of NAT1 and NAT2 mRNA expression between human tissue types may be of significance in assessing their contribution to known organ-specific toxicities of various arylamine drugs and carcinogens.

Five-year survival after first-ever stroke and related prognostic factors in the Perth Community Stroke Study

Background and Purpose-Few community-based studies have examined the long-term survival and prognostic factors for death within 5 years after an acute first-ever stroke. This study aimed to determine the absolute and relative survival and the independent baseline prognostic Factors for death over the next 5 years among all individuals and among 30-day survivors after a first-ever stroke in a population of Perth, Western Australia. Methods-Between February 1989 and August 1990, all individuals with a suspected acute stroke or transient ischemic attack of the brain who were resident in a geographically defined region of Perth, Western Australia, with a population of 138 708 people, were registered prospectively and assessed according to standardized diagnostic criteria. Patients were followed up prospectively at 4 months, 12 months, and 5 years after the index event. Results-Three hundred seventy patients with first-ever stroke were registered, and 362 (98%) were followed up at 5 years, by which time 210 (58%) had died. In the first year after stroke the risk of death was 36.5% (95% CI, 31.5% to 41.4%), which was 10-fold (95% CI, 8.3% to 11.7%) higher than that expected among the general population of the same age and sex. The most common cause of death was the index stroke (64%). Between 1 and 5 years after stroke, the annual risk of death was approximately 10% per year, which was approximately 2-fold greater than expected, and the most common cause of death was cardiovascular disease (41%). The independent baseline factors among 30-day survivors that predicted death over 5 years were intermittent clandication (hazard ratio [WR], 1.9; 95% CI, 1.2 to 2.9), urinary incontinence (HR, 2.0; 95% CI, 1.3 to 3.0), previous transient ischemic attack (HR, 2.4; 95% CT, 1.3 to 4.1), and prestroke Barthel Index <20/20 (HR, 2.0, 95% CI, 1.3 to 3.2). Conclusions-One-year survivors of first-ever stroke continue to die over the next 4 years at a rate of approximately 10% per year, which is twice the rate expected among the general population of the same age and sex. The most common cause of death is cardiovascular disease. Long-term survival after stroke may be improved by early, active, and sustained implementation of effective strategies for preventing subsequent cardiovascular events.

The development and evaluation of an incontinence screening questionnaire for female primary care

Although there is a high prevalence of leaking urine among Australian women, there are currently no standardized procedures for screening patients for incontinence in the primary care setting (known in Australia as general practice). In response to this, an incontinence screening questionnaire (ISQ) was developed and evaluated for use in general practice. Eighty-nine women completed an original compilation of 33 items that asked about situations associated with leaking urine, avoidance of leakage, and concern about leakage. Each item was assessed according to its acceptability for the population of female general practice patients, discriminative value, and test-retest reliability. These patients also underwent an objective test of incontinence, the 48-hour pad test, so that the screening items could be validated against an objective classification of incontinence. The study included women who had bladder control problems and those who did not. Eight items on the ISQ were shown to be acceptable to patients, discriminative, reliable, and valid indicators of objective incontinence. Five items were capable of predicting almost 70% of patients who showed objective leakage of urine and misclassified fewer than 15% of these patients. Those five items were selected for inclusion in the (refined) ISQ. (C) 2000 Wiley-Liss, Inc.

Effects of replacing meat with soyabean in the diet on sex hormone concentrations in healthy adult males

A randomised crossover dietary intervention study was performed to evaluate the effects of replacing meat protein in the diet with a soyabean product, tofu, on blood concentrations of testosterone, dihydrotestosterone, androstanediol glucuronide, oestradiol, sex hormone-binding globulin (SHBG), and the free androgen index (total testosterone concentration/SHBG concentration x 100; FAI). Forty-two healthy adult males aged 35-62 years were studied. Diets were isoenergetic, with either 150 g lean meat or 290 g tofu daily providing an equivalent amount of macronutrients, with only the source of protein differing between the two diets. Each diet lasted for 4 weeks, with a 2-week interval between interventions. Fasting blood samples were taken between 07.00 and 09.30 hours. Urinary excretion of genistein and daidzein was significantly higher after the tofu diet (P

Contraction of the pelvic floor muscles during abdominal maneuvers

Objective: To determine whether voluntary abdominal muscle contraction is associated with pelvic floor muscle activity. Design: Pelvic floor muscle activity was recorded during contractions of the abdominal muscles at 3 different intensities in supine and standing positions. Setting: Research laboratory. Participants: Six women and 1 man with no histories of lower back pain. Interventions: Not applicable. Main Outcome Measures: Electromyographic activity of the pelvic floor muscles was recorded with surface electrodes inserted into the anus and vagina. These recordings were corroborated by measurements of anal and vaginal pressures. Gastric pressure was recorded in 2 subjects. Results: Pelvic floor muscle electromyography increased with contraction of the abdominal muscles. With strong abdominal contraction, pelvic floor muscle activity did not differ from that recorded during a maximal pelvic floor muscle effort. The pressure recordings confirmed these data. The increase in pressure recorded in the anus and vagina preceded the pressure in the abdomen. Conclusions: In healthy subjects, voluntary activity in the abdominal muscles results in increased pelvic floor muscle activity. The increase in pelvic floor pressure before the increase in the abdomen pressure indicates that this response is preprogrammed. Dysfunction of the pelvic floor muscles can result in urinary and fecal incontinence. Abdominal muscle training to rehabilitate those muscles may be useful in treating these conditions.

Oxygen transport capacity in the air-breathing fish, Megalops cyprinoides: compensations for strenuous exercise

Tarpon have high resting or routine hematocrits (Hct) (37.6+/-3.4%) and hemoglobin concentrations (120.6+/-7.3 g 1(-1)) that increased significantly following bouts of angling-induced exercise (51.9+/-3.7% and 142.8+/-13.5 g 1(-1), respectively). Strenuous exercise was accompanied by an approximately tenfold increase in blood lactate and a muscle metabolite profile indicative of a high energy demand teleost. Routine blood values were quickly restored only when this facultative air-breathing fish was given access to atmospheric air. In vitro studies of oxygen transport capacity, a function of carrying capacity and viscosity, revealed that the optimal Hct range corresponded to that observed in fish under routine behaviour. During strenuous exercise however, further increase in viscosity was largely offset by a pronounced reduction in the shear-dependence of blood which conformed closely to an ideal Newtonian fluid. The mechanism for this behaviour of the erythrocytes appears to involve the activation of surface adrenergic receptors because pre-treatment with propranolol abolished the response. High levels of activity in tarpon living in hypoxic habitats are therefore supported by an elevated Hct with adrenergically mediated viscosity reduction, and air-breathing behaviour that enables rapid metabolic recovery. (C) 2002 Elsevier Science Inc. All rights reserved.

A randomized trial comparing hormone replacement therapy (HRT) and HRT plus calcitriol in the treatment of postmenopausal osteoporosis with vertebral fractures: Benefit of the combination on total body and hip density

We report a prospective, randomized, multi-center, open-label 2-year trial of 81 postmenopausal women aged 53-79 years with at least one minimal-trauma vertebral fracture (VF) and low (T-score below 2) lumbar bone mineral density (BMD). Group HRT received piperazine estrone sulfate (PES) 0.625 - 1.25 mg/d +/- medroxyprogesterone acetate (MPA) 2.5 - 5 mg/d,- group HRT/D received HRT plus calcitriol 0.25 mug bd. All with a baseline dietary calcium (Ca) of < I g/d received Ca carbonate 0.6 g nocte. Final data were on 66 - 70 patients. On HRT/D, significant (P < 0.001) BNID increases from baseline by DXA were at total body - head, trochanter, Ward's, total hip, inter-trochanter and femoral shaft (% group mean Delta 4.2, 6.1, 9.3. 3.7. 3.3 and 3.3%, respectively). On HRT, at these significant Deltas were restricted to the trochanter and sites. si Wards. Significant advantages of HRT/D over HRT were in BMD of total body (- head), total hip and trochanter (all P = 0.01). The differences in mean Delta at these sites were 1.3, 2.6 and 3.9%. At the following, both groups Improved significantly -lumbar spine (AP and lateral), forearm shaft and ultradistal tibia/fibula. The weightbearing, site - specific benefits of the combination associated with significant suppression of parathyroid hormone-suggest a beneficial effect on cortical bone. Suppression of bone turnover was significantly greater on HRT/D (serum osteocalcin P = 0.024 and urinary hydroxyproline/creatinine ratio P = 0.035). There was no significant difference in the number of patients who developed fresh VFs during the trial (HRT 8/36, 22%; HRT/D 4/34, 12% - intention to treat); likewise in the number who developed incident nonvertebral fractures. This Is the first study comparing the 2 treatments in a fracture population. The results indicate a significant benefit of calcitriol combined with HRT on total body BMD and on BNID at the hip, the major site of osteoporotic fracture.

Behavioural abnormalities of the hyposulphataemic Nas1 knock-out mouse

We recently generated a sodium sulphate cotransporter knock-out mouse (Nas1-/-) which has increased urinary sulphate excretion and hyposulphataemia. To examine the consequences of disturbed sulphate homeostasis in the modulation of mouse behavioural characteristics, Nas1-/- mice were compared with Nas1+/- and Nas1+/+ littermates in a series of behavioural tests. The Nas1-/- mice displayed significantly (P < 0.001) decreased marble burying behaviour (4.33 +/- 0.82 buried) when compared to Nas1+/+ (7.86 +/- 0.44) and Nas1+/- (8.40 +/- 0.37) animals, suggesting that Nas1-/- mice may have decreased object-induced anxiety. The Nas1-/- mice also displayed decreased locomotor activity by moving less distance (1.53 +/- 0.27 m, P < 0.05) in an open-field test when compared to Nas1+/+ (2.31 +/- 0.24 m) and Nas1+/- (2.15 +/- 0.19 m) mice. The three genotypes displayed similar spatiotemporal and ethological behaviours in the elevated-plus maze and open-field test, with the exception of a decreased defecation frequency by the Nas1-/- mice (40% reduction, P < 0.01). There were no significant differences between Nas1-/- and Nas1+/+ mice in a rotarod performance test of motor coordination and in the forced swim test assessing (anti-)depressant-like behaviours. This is the first study to demonstrate behavioural abnormalities in the hyposulphataemic Nas1-/- mice. (C) 2004 Elsevier B.V. All rights reserved.

NEURAL CORRELATES OF SCENT MARKING BEHAVIOR IN C57BL/6J MICE: DETECTION AND RECOGNITION OF A SOCIAL STIMULUS

Mice show urinary scent marking behavior as a form of social communication. Marking to a conspecific stimulus mouse or odor varies with stimulus familiarity, indicating discrimination of novel and familiar animals. This study investigated Fos immunoreactivity in inbred C57BL/6J (C57) males following scent marking behavior in response to detection of a social stimulus, or discrimination between a familiar and an unfamiliar conspecific. In Experiment 1 C57 mice were exposed for four daily trials to an empty chamber; on a test day they were exposed to the same chamber or to a male CD-1 mouse in that chamber. Increased scent marking to the CD-1 mouse was associated with increased Fos-immunoreactive cells in the basolateral amygdala, medial amygdala, and dorsal and ventral premammillary nuclei. In Experiment 2 C57 mice were habituated to a CD-1 male for 4 consecutive days and, on the 5th day, exposed to the same CD-1 male, or to a novel CD-1 male. Mice exposed to a novel CD-1 displayed a significant increase in scent marking compared to their last exposure to the familiar stimulus, indicating discrimination of the novelty of this social stimulus. Marking to the novel stimulus was associated with enhanced activation of several telencephalic, as well as hypothalamic and midbrain, structures in which activation had not been seen in the detection paradigm (Experiment 1). These included medial prefrontal and piriform cortices, and lateral septum; the paraventricular nuclei, ventromedial nuclei, and lateral area of the hypothalamus, and the ventrolateral column of the periaqueductal gray. These data suggest that a circumscribed group of structures largely concerned with olfaction is involved in detection of a conspecific olfactory stimulus, whereas discrimination of a novel vs. a familiar conspecific stimulus engages a wider range of forebrain structures encompassing higher-order processes and potentially providing an interface between cognitions and emotions. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.

Hematological parameters and anaerobic threshold in Brazilian soccer players throughout a training program

We assessed the responses of hematological parameters and their relationship to the anaerobic threshold of Brazilian soccer players during a training program. Twelve athletes were evaluated at the beginning (week 0, T1), in the middle (week 6, T2), and at the end (week 12, T3) of the soccer training program. On the first day at 7:30 AM, before collecting the blood sample at rest for the determination of the hematological parameters, the athletes were conducted to the anthropometric evaluation. On the second day at 8:30 AM, the athletes had their anaerobic threshold measured. Analysis of variance with Newman-Keuls`post hoc was used for statistical comparisons between the parameters measured during the soccer training program. Correlations between the parameters analyzed were determined using the Pearson`s correlation coefficient. Erythrocytes concentration, hemoglobin, and hematocrit were significantly increased from T1 to T2. The specific soccer training program led to a rise in erythrocytes, hemoglobin, and hematocrit from T1 to T2. We assumed that these results occurred due to the plasma volume reduction and may be explained by the soccer training program characteristics. Furthermore, we did not observe any correlation between the anaerobic threshold and the hematological parameters.